Bioactive agent release coating and controlled humidity method

• US 20070248637A1
• Filed: 08/19/2005
• Published: 10/25/2007
• Est. Priority Date: 06/18/2002
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Chappa, Ralph A., Ofstead, Ronald F., Tran, Linh V., Hergenrother, Robert W., Anderson, Aron B., Lawin, Laurie R.
• Granted Patent: US 7,833,548 B2
• Time in Patent Office: Days
• US Class Current: 424/422
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A coating composition in the form of a one or multi-part system, and method of applying such a composition under conditions of controlled humidity, for use in coating device surfaces to control and/or improve their ability to release bioactive agents in aqueous systems. The coating composition is particularly adapted for use with medical devices that undergo significant flexion and/or expansion in the course of their delivery and/or use, such as stents and catheters. The composition includes the bioactive agent in combination with a first polymer component such as polyalkyl(meth)acrylate, polyaryl(meth)acrylate, polyaralkyl(meth)acrylate, or polyaryloxyalkyl(meth)acrylate and a second polymer component such as poly(ethylene-co-vinyl acetate).

Claims

1-40. -40. (canceled)

41. A method for adjusting the rate of release of a bioactive agent from a coating composition provided in vivo, the method comprising the steps of:

a) providing the coating composition comprising a bioactive agent in combination with a plurality of polymers, including a first polymer component selected from the group consisting of polyalkyl(meth)acrylates and aromatic poly(meth)acrylates, and a second polymer component comprising poly(ethylene-co-vinyl acetate), and

b) altering a humidity level in which the coating composition is applied to a surface of a medical device to adjust the bioactive agent release profile, whereby increasing the humidity level accelerates the release of the bioactive agent and decreasing the humidity level decelerates the release of the bioactive agent.

42. A method according to claim 41 wherein the aromatic poly(meth)acrylates are selected from the group consisting of polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and humidity is altered by a method selected from the group consisting of controlling the humidity at which the device is coated with the coating composition, controlling the water content of the coating composition, or combinations thereof.

43. A method according to claim 41 wherein the first polymer component is selected from the group consisting of:

a) polyalkyl(meth)acrylates with an alkyl chain length from 2 to 8 carbons,

b) polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates with aryl groups having from 6 to 16 carbon atoms, the first polymer component having a weight average molecular weight of about 50 to about 900 kilodaltons, and wherein the vinyl acetate concentrations are between about 20% and about 40% by weight.

44. A method according to claim 41 wherein the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives, anticancer chemotherapeutic agents, anti-inflammatory steroid or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

45. A method according to claim 41, the concentration of bioactive agent being about 0.01 to about 90 percent, by weight, based on the weight of the coating composition.

46. A method according to claim 41, the coating composition thickness being about 0.1 micrometers to about 100 micrometers.

47. A method for adjusting the rate of release of a bioactive agent from a coating composition provided in vivo, the method comprising the steps of:

a) providing the coating composition comprising a bioactive agent in combination with a plurality of polymers, including a first polymer component selected from the group consisting of polyalkyl(meth)acrylates and aromatic poly(meth)acrylates, and a second polymer component comprising poly(ethylene-co-vinyl acetate), and

b) accelerating the release of the bioactive agent in vivo by increasing a humidity level in which the coating composition is applied to a surface of a medical device.

48. A method according to claim 47 wherein the aromatic poly(meth)acrylates are selected from the group consisting of polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and humidity is altered by a method selected from the group consisting of controlling the humidity at which the device is coated with the coating composition, controlling the water content of the coating composition, or combinations thereof.

49. A method according to claim 47 wherein the first polymer component is selected from the group consisting of:

a) polyalkyl(meth)acrylates with an alkyl chain length from 2 to 8 carbons,

b) polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates with aryl groups having from 6 to 16 carbon atoms, the first polymer component having a weight average molecular weight of about 50 to about 900 kilodaltons, and wherein the vinyl acetate concentrations are between about 20% and about 40% by weight.

50. A method according to claim 47 wherein the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives, anticancer chemotherapeutic agents, anti-inflammatory steroid or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

51. A method according to claim 47, the concentration of bioactive agent being about 0.01 to about 90 percent, by weight, based on the weight of the coating composition.

52. A method according to claim 47, the coating composition thickness being about 0.1 micrometers to about 100 micrometers.

53. A method for adjusting the rate of release of a bioactive agent from a coating composition provided in vivo, the method comprising the steps of:

a) providing the coating composition comprising a bioactive agent in combination with a plurality of polymers, including a first polymer component selected from the group consisting of polyalkyl(meth)acrylates and aromatic poly(meth)acrylates, and a second polymer component comprising poly(ethylene-co-vinyl acetate), and

b) decelerating the release of the bioactive agent in vivo by decreasing the humidity level in which the coating composition is applied to a surface of a medical device.

54. A method according to claim 53 wherein the aromatic poly(meth)acrylates are selected from the group consisting of polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates, and humidity is altered by a method selected from the group consisting of controlling the humidity at which the device is coated with the coating composition, controlling the water content of the coating composition, or combinations thereof.

55. A method according to claim 53 wherein the first polymer component is selected from the group consisting of:

a) polyalkyl(meth)acrylates with an alkyl chain length from 2 to 8 carbons,

b) polyaryl(meth)acrylates, polyaralkyl(meth)acrylates, and polyaryloxyalkyl(meth)acrylates with aryl groups having from 6 to 16 carbon atoms, the first polymer component having a weight average molecular weight of about 50 to about 900 kilodaltons, and wherein the vinyl acetate concentrations are between about 20% and about 40% by weight.

56. A method according to claim 53 wherein the bioactive agent is selected from the group consisting of thrombin inhibitors, antithrombogenic agents, thrombolytic agents, fibrinolytic agents, vasospasm inhibitors, calcium channel blockers, vasodilators, antihypertensive agents, antimicrobial agents, antibiotics, inhibitors of surface glycoprotein receptors, antiplatelet agents, antimitotics, microtubule inhibitors, anti secretory agents, actin inhibitors, remodeling inhibitors, antisense nucleotides, anti metabolites, antiproliferatives, anticancer chemotherapeutic agents, anti-inflammatory steroid or non-steroidal anti-inflammatory agents, immunosuppressive agents, growth hormone antagonists, growth factors, dopamine agonists, radiotherapeutic agents, peptides, proteins, enzymes, extracellular matrix components, inhibitors, free radical scavengers, chelators, antioxidants, anti polymerases, antiviral agents, photodynamic therapy agents, and gene therapy agents.

57. A method according to claim 53, the concentration of bioactive agent being about 0.01 to about 90 percent, by weight, based on the weight of the coating composition.

58. A method according to claim 53, the coating composition thickness being about 0.1 micrometers to about 100 micrometers.